Age-Period-Cohort Modeling of Multiple Sclerosis Incidence Rates in Kuwait: 1980–2014

Abstract

Background: Multiple sclerosis (MS) is a complex immune-mediated disorder of the central nervous system with undefined etiology. Genetic predisposition and environmental factors play an imperative role in MS causation and its sustained increasing burden worldwide. This study examined the age, period, and cohort effects on MS incidence rates in Kuwait. Methods: In this retrospective cohort study, data on MS cases diagnosed between January 1, 1980 and December 31, 2014 and registered in National MS Registry and reference population were obtained. Age-period-cohort (APC) analysis was conducted using a loglinear Poisson regression model to supplement the descriptive and graphical presentation. Descriptive statistics were complemented with APC parameters’ estimates including net drift, local drift, age at onset curve, and longitudinal age trend. Age effect was presented as incidence rates (per 10⁵ person-years), whereas period and cohort effects were presented as adjusted relative rates. Results: A total of 1,131 cases were diagnosed in 1,385,923 person-years. Overall age-standardized MS incidence rate was 64.5 (95% CI 52.4–79.8). An estimated annual percentage change revealed 7.4% annual increase in MS incidence rate during the study period (Net drift = 7.4%; 95% CI 4.1–10.8%). APC “fitted” age-at-onset curve showed a bimodal pattern with peaked incidence rates at 20–24 years and 45–49 years of age. Compared with the referent period (1980–1984) and cohort (1970–1974), MS incidence rates progressively and significantly (p < 0.001) increased during subsequent time periods and in successive cohorts. Results of APC analysis are descriptive in nature and specific etiological hypotheses were not evaluated. However, the findings of this study substantiated the notion of multiplicity of genetic and/or environmental risk factors’ contributions. Conclusion: A substantial increase in MS incidence rates was recorded, which significantly varied in all 3 temporal dimensions during the study period. Future studies may contemplate biological basis for recorded temporal increase in MS risk.